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KLF2 Transcription-Factor Deficiency in T Cells Results in Unrestrained Cytokine Production and Upregulation of Bystander Chemokine Receptors
Open accessAbstract
SUMMARY The transcription factor KLF2 regulates T cell trafficking by promoting expression of the lipid binding receptor, S1P1, and the selectin, CD62L. Recently, it was proposed that KLF2 also represses the expression of chemokine receptors. We confirm the upregulation of the chemokine receptor CXCR3 on KLF2 deficient T cells. However, we show that this is a cell nonautonomous effect, as revealed by CXCR3 upregulation on WT bystander cells in mixed bone marrow chimeras with KLF2 deficient cells. Furthermore, we show that KLF2 deficient T cells overproduce IL-4, leading to the upregulation of CXCR3 through an IL-4 receptor and eomesodermin dependent pathway. Consistent with the increased IL-4 production, we find high levels of serum IgE in mice with T cell specific KLF2 deficiency. Our findings support a model where KLF2 regulates T cell trafficking by direct regulation of S1P1 and CD62L, and restrains spontaneous cytokine production in naive T cells.
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Cites
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L., & Cyster, J. G. (2004) · Nature · doi:10.1038/nature02284 · Cited by 2,581
CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs
Shiow, L. R., Rosen, D. B., Brdičková, N., Xu, Y., An, J., Lanier, L. L., Cyster, J. G., & Matloubian, M. (2006) · Nature · doi:10.1038/nature04606 · Cited by 1,189
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Mammalian Krüppel-Like Factors in Health and Diseases
McConnell, B. B., & Yang, V. W. (2010) · Physiological Reviews · doi:10.1152/physrev.00058.2009 · Cited by 1,018
Skon, C. N., Lee, J.-Y., Anderson, K. G., Masopust, D., Hogquist, K. A., & Jameson, S. C. (2013) · Nature Immunology · doi:10.1038/ni.2745 · Cited by 817
Self-citationSphingosine-1-Phosphate and Lymphocyte Egress from Lymphoid Organs
Cyster, J. G., & Schwab, S. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075011 · Cited by 815
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Gattinoni, L., Klebanoff, C. A., & Restifo, N. P. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3322 · Cited by 599
Peripheral CD4+ T‐cell differentiation regulated by networks of cytokines and transcription factors
Zhu, J., & Paul, W. E. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00951.x · Cited by 579
Metadata
- Authors
- Weinreich, M. A., Takada, K., Skon, C., Reiner, S. L., Jameson, S. C., & Hogquist, K. A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 31
- Issue
- 1
- Pages
- 122-130
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2002549598
- Cited by
- 249
- References
- 2
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Weinreich, M. A., Takada, K., Skon, C., Reiner, S. L., Jameson, S. C., & Hogquist, K. A. (2009). KLF2 Transcription-Factor Deficiency in T Cells Results in Unrestrained Cytokine Production and Upregulation of Bystander Chemokine Receptors. Immunity. https://doi.org/10.1016/j.immuni.2009.05.011
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